Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukaemia: a randomised phase II trial from HOVON, the Dutch-Belgian Haemato-Oncology Working Group for adults.

Daenen, Simon;van der Holt, Bronno;Verhoef, Gregor E G;Löwenberg, Bob;Sonneveld, Pieter;et.al.
(2004) Leukemia Research : clinical and laboratory studies — Vol. 28, n° 10, p. 1057-1067 (2004)

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Authors
  • Daenen, Simon
    Author
  • van der Holt, Bronno
    Author
  • Verhoef, Gregor E G
    Author
  • Löwenberg, Bob
    Author
  • Ferrant, AugustinUCLouvain
    Author
  • Sonneveld, Pieter
    Author
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Abstract
Cyclosporin A (CsA) inhibits the P-gp pump that can be responsible for failure of cytostatic treatment in acute myeloid leukaemia (AML). Eighty patients with relapsing/refractory AML were randomly assigned to mitoxantrone (M) and etoposide (VP) (MVP) in unmitigated antileukaemic doses with or without CsA, to investigate if toxicity was manageable and if antileukaemic therapy could be improved. CsA did not delay haematological recovery, but fewer CsA patients received post-induction therapy because of haematological and non-haematological toxicity. CR rate was 43% for MVP and 53% for CsA; DFS was 9 and 8 months, and OS 8 and 9 months, respectively. Seventeen of 38 CR patients proceeded to stem cell transplantation (SCT). After a median follow-up of 66 months, six patients were still alive. Addition of CsA did not improve treatment outcome, possibly due to inadequate post-induction therapy as a result of increased toxicity.
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Daenen, S., van der Holt, B., Verhoef, G. E. G., Löwenberg, B., Wijermans, P. W., Huijgens, P. C., van Marwijk Kooy, R., Schouten, H. C., Kramer, M. H. H., Ferrant, A., van den Berg, E., Steijaert, M. M. C., Verdonck, L. F., & Sonneveld, P. (2004). Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukaemia: a randomised phase II trial from HOVON, the Dutch-Belgian Haemato-Oncology Working Group for adults. Leukemia Research : clinical and laboratory studies, 28(10), 1057-1067. https://doi.org/10.1016/j.leukres.2004.03.001 (Original work published 2004)